Development of a Yeast Bio-Assay to Screen Anti-Mitochondrial Drugs

Johan   L.F.   Kock; Chantel   W.   Swart; Desmond   M.   Ncango; Johan   L.F.   Kock Jr.; Ingrid   A.   Munnik; Marleen   M.J.   Maartens; Carolina   H.   Pohl; Pieter   W.J.   van Wyk

Abstract

Previous studies show that acetylsalicylic acid (aspirin) at low concentrations affects yeast sexual structure development in a similar fashion than oxygen depletion. This is ascribed to its anti-mitochondrial action. In this study, we report the same for other anti-inflammatory (i.e. ibuprofen, indomethacin, salicylic acid, benzoic acid) as well as anticancer (Lonidamine) drugs, also known for inhibiting mitochondrial activity in mammalian cells. This is shown by a unique yeast bio-assay, with the mitochondrion-dependent sexual structure, riboflavin production, and hyphal morphology of the yeast Eremothecium ashbyi serving as indicators. These drugs affect this yeast in a similar way as found under oxygen limitation conditions by inhibiting sexual structure development (most sensitive), riboflavin production, and yielding characteristically wrinkled and granular hyphae, presenting a unique “anoxic” morphological pattern for this yeast. Only drugs associated with anti-mitochondrial activity presented such a pattern. This bio-assay may find application in the screening for novel drugs from various sources with anti-mitochondrial actions.

Keywords: Anticancer, antifungal, anti-inflammatory, anti-mitochondrion, bio-assay, yeast